Oncology Flashcards
What are cancer cells?
Cells which undergo uncontrolled and unregulated cell proliferation with the ability to metastasise to other places in the body.
What are the twelve characteristics of cancer cells that underline their behaviour?
- Self sufficiency in growth signals
- Insensitivity to anti-growth signals
- Evading apoptosis
- Limitless replicative potential
- Sustained angiography
- Tissue invasion and metastasis
- Dysregulating metabolism
- Evading the immune system
- Genome instability
- Inflammation
Where in the cell cycle do cytotoxic chemotherapy agents target?
Depends on how the agent works.
More rapidly growing tumours have more cycles and therefore more G1, S, and G2 phases.
So a drug specific for DNA synthesis (S) stage is most effective against rapidly growing tumours.
Define pharmacokinetics.
What the body does to the drug.
Define pharmacodynamics.
What the drug does to the body.
What are the main principles of cancer drug treatment?
The drug must reach the cancer cells
Cell must be sensitive to the cytotoxic of drug
Toxic effect must be minimal to the benefit of the drug
What is screening?
A process of identifying apparently health people who may be at increased risk of a disease or conditions.
How is the grade of a tumour determined?
The extent to which the neoplasm resembles its cell or tissue of origin.
How are malignant tumours graded?
Well, moderately, or poorly differentiated.
How are benign tumours graded?
They are not, as they closely resemble their parent tissue.
Which tumours grow slowly?
Well differentiated
What does the stage of a cancer describe?
The size of the tumour and the extent to which it has spread
What are the components of the TNM staging classification?
Tumour
Nodes
Metastases
What does TNM stage IV generally represent?
Metastases to distant organs
For which tumours is systemic anticancer treatment given alone, with radical intent?
Germ cell tumours
Haematological cancers
What do “neoadjuvant” and “adjuvant” mean?
Neoadjuvant - perioperative period, pre surgery
Adjuvant - perioperative, post surgery
Why does surgical resection of early tumours not cure some patients?
Presence of micrometastases which can cause recurrence.
How does neoadjuvant chemotherapy offer survival benefit?
Eradicated micrometastatic disease
What are the risks of neoadjuvant chemotherapy?
Risks a potentially fatal chemotherapy related complication.
Decreases the patients performance prior to curative surgery
Why is adjuvant chemotherapy given?
Ensures any margins or micrometastatic sites are free from disease
What is radiotherapy?
The administration of ionizing radiation with the intent of killing the cancer cell or prevent it from replicating.
How does radiotherapy work?
Ionizing - ionizes cells causing apoptosis
Non-ionizing (X-Rays) - formation of free radicals and reactive oxygen species. These interact with the covalent bonds of DNA and can result in apoptosis.
How is radiotherapy delivered?
External to the body
Internal to the body (brachytherapy)
Systemically (iodine-131)
What is the radiation dose measured in?
Grays - Gy
The amount of radiation absorbed by each kilogram of tissue
What are the acute side effects of radiotherapy?
Nausea, vomiting, anorexia Acute radiation dermatitis Mucositis Oesophagitis Diarrhoea
Name three types of systemic anti-cancer treatment.
Cytotoxic chemotherapy
Hormone therapy
Molecularly targeted therapy
How are cytotoxic chemotherapies classified?
Alkylating agents
Antimetabolites
Natural products
How do alkylating agents work?
Add an alkyl group to the guanine base of DNA, preventing DNA replication and RNA transcription.
Not phase specific i.e. can occur at any point in the cell cycle
How do antimetabolites work?
Inhibit enzymes or metabolites involved in DNA or RNA synthesis
Name two alkylating agents
Cisplatin
Cyclophosphamide
Name two antimetabolites
Methotrexate
Fluorouracil
Name two natural products
Bleomycin
Doxorubicin
What are some problems with chemotherapy?
Variable efficacy secondary to tumour biology/intrinsic resistance
Acquired resistance
Toxic side effects
What are general side effects of chemotherapy related to?
Rapidly dividing cells
Name some general side effects of chemotherapy.
Nausea and vomiting
Alopecia
Skin rashes
Constipation
Name some other specific side effects of chemotherapy?
Cardiomyopathy
Renal impairment
Infertility
Define hypercalcaemia.
Corrected calcium >2.6mmol/L
40% of circulating calcium is bound to what?
Albumin
How do you correct calcium levels?
Add 0.1mmol/L to calcium, for every 4g/L that albumin levels are below 40g/L
This allows for changes in serum albumin levels
What are the main causes of hypercalcaemia?
Hyperparathyroidism
Malignancy - bone mets or parathyroid hormone related peptide secretion
Thyrotoxicosis
How does hypercalcaemia present?
Bones, stones, groans, and psychic moans
Abdo pain, constipation, vomiting
Polyuria and polydipsia
Confusion and fatigue
Depression
What are the important investigations for hypercalcaemia?
PTH
ECG
Imaging for bone mets if appropriate
What is seen on ECG in hypercalcaemia?
Shortened QT interval
What is the initial acute management of hypercalcaemia?
Diagnose underlying cause
Correct dehydration with 0.9% saline
What is the further management of hypercalcaemia following rehydration?
IV bisphosphonates e.g. pamidronate
Inhibits osteoclasts and reduces bone turnover, reduces calcium over several days
What is the treatment of persistent or relapsed hypercalcaemia of malignancy?
Denosumab (inhibits RANK ligand)
What does the SVC drain?
The head, neck, upper limbs, and upper thorax
What are the causes of SVC obstruction?
Thrombus
Direct tumour invasion inside and outside the vessel wall
Which tumours can invade the SVC?
Lung cancer
Lymphoma
Germ cell tumours
ALL
What are the symptoms of SVC obstruction?
May be sudden or gradual Dyspnoea Chest pain at rest Cough Neck, face, and arm swelling Nasal stuffiness Visual disturbance
What are the signs of SVC obstruction?
Dilated veins and oedema over arms, neck, and anterior chest wall
Severe respiratory distress
Cyanosis
Engorged conjunctiva
How is SVC obstruction diagnosed?
Clinical
CXR - widened mediastinum/mass
CT
How is SVC obstruction managed?
Elevation of the head, oxygen
High dose dexamethasone
Endovascular stenting
What is the name of the condition caused by abrupt release of large quantities of cellular components into the blood following rapid lysis of the malignant cell?
Tumour lysis syndrome
What are the risk factors for tumour lysis syndrome?
Volume depletion
Renal impairment
Treatment sensitive tumours
High pre-treatment urate, lactate, and LDH
What are the most common malignancies for tumour lysis syndrome?
Haematological
How does tumour lysis syndrome present?
Weakness
Paralytic ileus - constipation, vomiting, abdo pain
Cardiac arrhythmias - palpitations, chest pain
Seizures
AKI
What are the metabolic abnormalities of tumour lysis syndrome?
Hyperuricaemia Hyperphosphataemia Hyperkalaemia Hypocalcaemia AKI
How does tumour lysis syndrome cause renal impairment?
Deposition of uric acid and calcium phosphate crystals in renal tubules can cause acute renal failure
How is tumour lysis syndrome prevented?
IV fluids
Allopurinol
Rasburicase
How does allopurinol work?
Xanthine oxidase inhibitor
Blocks conversion of xanthines to uric acid
How does rasburicase work?
Recombinant urate oxidase
Catalyses the oxidation of uric acid to allantoin which is much more soluble
How is tumour lysis syndrome treated?
Vigorous hydration Correct high potassium Rasburicase (stop allopurinol) Acetazolamide Phosphate binders Dialysis
How is potassium corrected in tumour lysis syndrome?
10mls 10% calcium gluconate IV if potassium >7mmol/L or ECH changes
IV insulin and dextrose
Salbutamol 2.5mg nebulizer
Which patients are at risk of neutropenic sepsis?
Neutrophil count below 1x10^9/L
When should patients be treated for neutropenic sepsis?
Oral temperature >38 degrees OR
Two consecutive readings of >37.5 degrees for two hours
AND an absolute neutrophil count <1x10^9/L
How is neutropenic sepsis diagnosed?
Septic screen
Clinically relevant swabs or cultures
What are the antibiotic guidelines for neutropenic sepsis?
Piperacillin with tazobactam - tazocin
How is neutropenic sepsis prevented against?
Fluoroquinolone or granulocyte colony stimulating factor in some cases
Where does the spinal cord run to and from?
The base of the skull to L1
What does the cauda equina contain?
Extends below L1 and contains the lumbar, sacral, and coccygeal spinal nerves
What is the most common cause of spinal cord compression?
Secondary malignancy
What are the other causes of spinal cord compression?
Trauma
Disc prolapse
RA
Spinal infection
How does spinal cord compression present?
Radicular pain
Limb weakness below the level of compression
Sensory loss below level of compression (sensory level present)
Bladder or bowel dysfunction
How is spinal cord compression diagnosed?
MRI whole spine
How is spinal cord compression treated?
Analgesia
High dose steroids
Spinal decompression
Radiotherapy
